Sea slug genes ooze a path toward understanding human pain

One of the weird things about chronic pain is that it can sometimes be more “in your brain” than, say “in your back” or “in your elbow“. Take for example, a phenomenon known as phantom limb pain – where individuals who lose a limb, can still complain of feeling pain in that very missing limb. As described here, it is possible to “unlearn” this pain – which is a learning process involving changes in synaptic connectivity in the brain.

Where then, and how, might pain and learning related to chronic pain be happening “in your brain” rather than in your back or elbow. Well, a recent paper from Min Zhuo’s lab at the University of Toronto have reported some new insights into synaptic mechanisms of pain. In their recent paper [doi:10.1186/1744-8069-4-40], “Enhancement of presynapticglutamate release and persistent inflammatory pain by increasing neuronal cAMP in the anterior cingulate cortex” they evaluate the role of presynaptic glutamamte release in a brain region known as the anterior cingulate cortex – a region whose activity is well-known to correlate with reports of pain.

One of the cool tricks they used to evaluate the role of pre- vs. post-synaptic actions of glutamate was to use mice that carry a G-protein coupled receptor from the sea slug (Aplysia) which can respond to octopamine (a chemical not normally found in mouse brains) to activate glutamate release pre-synaptically. When mice were administered octopamine in the cingulate cortex, became more sensitive to chronic pain. This identifies a very specific biochemical pathways and brain area for which pharmacologic and behavioral therapeutics might be designed for the treatment of chronic pain.